Abstract
Biological characteristics of nodule-like alveolar lesions (NLAL) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in organ culture of whole mammary gland (BALB/c female mice) were assessed after transplantation into gland-free mammary fat pads of syngeneic virgin mice. (i) Tissue-fragment explants from NLAL areas of the gland produced abnormal lobuloalveolar (LA) outgrowths in 3 of 10 fat pads. (ii) Transplantation of dissociated cells of NLAL-derived LA outgrowths into 36 fat pads showed 100% LA outgrowths and 3 (8%) of these 36 outgrowths produced mammary carcinomas. (iii) The explants of dissociated cells from whole mammary glands treated with DMBA in culture produced full or partial LA structures in 2 of 56 outgrowths. (iv) The explants of dissociated cells prepared from outgrowths derived from outgrowths derived from explants as in iii produced 9 LA outgrowths in 16 instances; mammary tumor incidence in these outgrowths was 3 of 16 (18%). (v) The explants of tissue fragments from LA outgrowths as in iv produced LA outgrowths in 20 of 20 fat pads; mammary carcinomas appeared in 16 of 20 (80%) of these outgrowths. No NLAL was detectable in control glands treated with dimethyl sulfoxide (solvent for DMBA); explants of the control glands consistently produced ductal outgrowths and no tumor. This accomplishment of chemical carcinogen-induced neoplastic transformation of epithelial cells in vitro provides a model for studying carcinogenesis in an entire isolated organ.
Full text
PDF![5886](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39de/411757/ad08d6eafdae/pnas00011-0480.png)
![5887](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39de/411757/48b055479cfd/pnas00011-0481.png)
![5888](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39de/411757/a0c50244db2c/pnas00011-0482.png)
![5889](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39de/411757/3533ac641bd7/pnas00011-0483.png)
![5890](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39de/411757/7c8a9d8de8eb/pnas00011-0484.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Banerjee M. R. Responses of mammary cells to hormones. Int Rev Cytol. 1976;47:1–97. doi: 10.1016/s0074-7696(08)60086-8. [DOI] [PubMed] [Google Scholar]
- Banerjee M. R., Terry P. M., Sakai S., Lin F. K. Regulation of messenger RNA and specific milk protein in mammary gland. J Toxicol Environ Health. 1977 Sep;3(1-2):281–308. doi: 10.1080/15287397709529566. [DOI] [PubMed] [Google Scholar]
- Banerjee M. R., Wood B. G., Washburn L. L. Chemical carcinogen-induced alveolar nodules in organ culture of mouse mammary gland. J Natl Cancer Inst. 1974 Nov;53(5):1387–1393. doi: 10.1093/jnci/53.5.1387. [DOI] [PubMed] [Google Scholar]
- Casto B. C., DiPaolo J. A. Virus, chemicals and cancer. Prog Med Virol. 1973;16:1–47. [PubMed] [Google Scholar]
- DEOME K. B., FAULKIN L. J., Jr, BERN H. A., BLAIR P. B. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res. 1959 Jun;19(5):515–520. [PubMed] [Google Scholar]
- Daniel C. W., De Ome K. B., Young J. T., Blair P. B., Faulkin L. J., Jr The in vivo life span of normal and preneoplastic mouse mammary glands: a serial transplantation study. Proc Natl Acad Sci U S A. 1968 Sep;61(1):53–60. doi: 10.1073/pnas.61.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dao T. L., Sinha D. Mammary adenocarcinoma induced in organ culture by 7,12-dimethylbenz(a)anthracene. J Natl Cancer Inst. 1972 Aug;49(2):591–593. [PubMed] [Google Scholar]
- DeOme K. B., Miyamoto M. J., Osborn R. C., Guzman R. C., Lum K. Detection of inapparent nodule-transformed cells in the mammary gland tissues of virgin female BALB/cfC3H mice. Cancer Res. 1978 Jul;38(7):2103–2111. [PubMed] [Google Scholar]
- Dickens M. S., Custer R. P., Sorof S. Retinoid prevents mammary gland transformation by carcinogenic hydrocarbon in whole-organ culture. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5891–5895. doi: 10.1073/pnas.76.11.5891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heidelberger C. Chemical carcinogenesis. Annu Rev Biochem. 1975;44:79–121. doi: 10.1146/annurev.bi.44.070175.000455. [DOI] [PubMed] [Google Scholar]
- Heidelberger C. Chemical oncogenesis in culture. Adv Cancer Res. 1973;18:317–366. doi: 10.1016/s0065-230x(08)60756-3. [DOI] [PubMed] [Google Scholar]
- Ichinose R. R., Nandi S. Influence of hormones on lobulo-alveolar differentiation of mouse mammary glands in vitro. J Endocrinol. 1966 Aug;35(4):331–340. doi: 10.1677/joe.0.0350331. [DOI] [PubMed] [Google Scholar]
- Kundu A. B., Telang N. T., Banerjee M. R. Binding of 7,12-dimethylbenz[a]anthracene to BALB/c mouse mammary gland DNA in organ culture. J Natl Cancer Inst. 1978 Aug;61(2):465–469. [PubMed] [Google Scholar]
- LASNITZKI I. GROWTH PATTERN OF THE MOUSE PROSTATE GLAND IN ORGAN CULTURE AND ITS RESPONSE TO SEX HORMONES, VITAMIN A, AND 3-METHYLCHOLANTHRENE. Natl Cancer Inst Monogr. 1963 Oct;12:381–403. [PubMed] [Google Scholar]
- Lin F. K., Banerjee M. R., Crump L. R. Cell cycle-related hormone carcinogen interaction during chemical carcinogen induction of nodule-like mammary lesions in organ culture. Cancer Res. 1976 May;36(5):1607–1614. [PubMed] [Google Scholar]
- Medina D. Mammary tumorigenesis in chemical carcinogen-treated mice. I. Incidence in BALB-c and C57BL mice. J Natl Cancer Inst. 1974 Jul;53(1):213–221. doi: 10.1093/jnci/53.1.213. [DOI] [PubMed] [Google Scholar]
- Medina D. Mammary tumorigenesis in chemical carcinogen-treated mice. II. Dependence on hormone stimulation for tumorigenesis. J Natl Cancer Inst. 1974 Jul;53(1):223–226. doi: 10.1093/jnci/53.1.223. [DOI] [PubMed] [Google Scholar]
- Medina D., Shepherd F., Gropp T. Enhancement of the tumorigenicity of preneoplastic mammary nodule lines by enzymatic dissociation. J Natl Cancer Inst. 1978 May;60(5):1121–1126. doi: 10.1093/jnci/60.5.1121. [DOI] [PubMed] [Google Scholar]
- Mehta R. G., Banerjee M. R. Action of growth-promoting hormones on macromolecular biosynthesis during lobulo-alveolar development of the entire mammary gland in organ culture. Acta Endocrinol (Copenh) 1975 Nov;80(3):501–516. doi: 10.1530/acta.0.0800501. [DOI] [PubMed] [Google Scholar]
- Richards J., Nandi S. Neoplastic transformation of rat mammary cells exposed to 7,12-dimethylbenz[alpha]anthracene or N-nitrosomethylurea in cell culture. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3836–3840. doi: 10.1073/pnas.75.8.3836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Röller M. R., Heidelberger C. Attempts to produce carcinogenesis in organ cultures of mouse prostate with polycyclic hydrocarbons. Int J Cancer. 1967 Sep 15;2(5):509–520. doi: 10.1002/ijc.2910020513. [DOI] [PubMed] [Google Scholar]
- Terry P. M., Banerjee M. R., Lui R. M. Hormone-inducible casein messenger RNA in a serum-free organ culture of whole mammary gland. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2441–2445. doi: 10.1073/pnas.74.6.2441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tonelli Q. J., Custer R. P., Sorof S. Transformation of cultured mouse mammary glands by aromatic amines and amides and their derivatives. Cancer Res. 1979 May;39(5):1784–1792. [PubMed] [Google Scholar]
- Williams G. M., Weisburger E. K., Weisburger J. H. Isolation and long-term cell culture of epithelial-like cells from rat liver. Exp Cell Res. 1971 Nov;69(1):106–112. doi: 10.1016/0014-4827(71)90316-8. [DOI] [PubMed] [Google Scholar]
- Wood B. G., Washburn L. L., Mukherjee A. S., Banerjee M. R. Hormonal regulation of lobulo-alveolar growth, functional differentiation and regression of whole mouse mammary gland in organ culture. J Endocrinol. 1975 Apr;65(1):1–6. doi: 10.1677/joe.0.0650001. [DOI] [PubMed] [Google Scholar]
- Yamada T., Takoka T., Katsuta H., Namba M., Sato J. Carcinogenesis in tissue culture. 20. Electrokinetic changes in cultured rat liver cells associated with malignant transformation in vitro. Jpn J Exp Med. 1972 Aug;42(4):377–388. [PubMed] [Google Scholar]